SCI Consortium Study: Neural Stem Cell Transplantation for Cervical Spinal Cord Injury

SCI 联盟研究：神经干细胞移植治疗颈脊髓损伤

• 批准号: 10385724
• 负责人: JOHN H. BROCK
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385724
• 关键词: Acute; Adult; American; Anatomy; Animal Model; Animals; Axon; Brain; Cell Line; Cells; Cervical; Cervical spinal cord injury; Cervical spinal cord structure; Chronic; Clinical; Contusions; Data; Development; Evaluation; Evolution; Extracellular Matrix; Goals; Healthcare Systems; Human; Human Cell Line; Human Development; Implant; Infection; Injury; Interneurons; Lead; Learning; Lesion; Longitudinal Studies; Maps; Modeling; Modification; Motor; Motor Neurons; Nature; Neuroglia; Neurons; Nude Rats; Outcome; Output; Phenotype; Rabies; Rabies virus; Rattus; Recovery; Research; Research Project Grants; Rodent; Safety; Sensory; Signal Transduction; Site; Spinal; Spinal Cord; Spinal Cord Contusions; Spinal Cord transection injury; Spinal cord injury; Stem cell transplant; Synapses; Techniques; Testing; Time; TimeLine; Translations; Transplantation; Variant; Veterans; Work; axon guidance; base; cell type; cellular targeting; central gray matter; clinical translation; clinically relevant; clinically translatable; collaborative environment; economic impact; functional outcomes; human embryonic stem cell line; improved; injury and repair; innovation; lead candidate; nerve stem cell; nerve supply; neural circuit; neurodevelopment; novel; novel strategies; novel therapeutics; programs; relating to nervous system; severe injury; stem cell biology; stem cell therapy; synaptogenesis; white matter

Spinal cord injury (SCI) often damages, not only white matter axon tracts that transmits signals to and from the brain, but also the central gray matter, causing segmental loss of interneurons and motor neurons. Transplantation of neural stem cells (NSCs) has the potential to replace lost neurons and glia. These transplanted neurons can form functional relays between spinal segments disconnected by the injury. We have generated human NSCs with a spinal cord identity to test the hypothesis that spinal cord NSCs will more appropriately integrate into sites of the injured spinal cord. Our preliminary data provide evidence that both rat and human neural stem cells can be transplanted into multiple models of SCI, including a clinically relevant contusion model. However, humans NSCs appear to develop on a longer timeline, more similar to human development. Therefore, we aim to characterize the maturation and phenotype of human spinal cord NSCs (scNSCs). Long-term studies will assess the efficacy, safety and synaptic integration of such scNSC therapy in a clinically relevant contusive model of cervical SCI. This work is highly innovative and clinically oriented: 1) We will utilize a contusion type injury that is most applicable to human SCI. 2) We will examine a novel human NSC line with a spinal cord identity (scNSCs). 3) Long-term studies will examine the maturation, efficacy and safety of scNSCs, our lead cell candidate, for the treatment of spinal cord injury. 4) Novel trans-synaptic tracing techniques will be used to assess the synaptic integration of both host inputs to the graft and graft outputs to host motor neurons.

脊髓损伤（SCI）不仅损害传递信号的白色轴突束， 从大脑，而且中央灰质，造成节段性损失的中间神经元和运动 神经元神经干细胞（NSC）的移植有可能取代失去的神经元， 神经胶质。这些移植的神经元可以在断开的脊髓节段之间形成功能中继 的伤害。我们已经产生了具有脊髓特性的人类NSC，以测试以下假设： 脊髓NSC将更适当地整合到受损脊髓的部位。我们 初步数据提供了证据，大鼠和人类神经干细胞都可以移植到 SCI的多种模型，包括临床相关挫伤模型。然而，人类神经干细胞 似乎在更长的时间轴上发展，更类似于人类的发展。因此，我们的目标是 表征人脊髓NSC（scNSC）的成熟和表型。长期研究 将评估这种scNSC疗法在临床上的疗效、安全性和突触整合。 颈椎脊髓损伤的相关挫伤模型。 这项工作是高度创新和临床导向： 1)我们将使用最适用于人类SCI的挫伤型损伤。 2)我们将研究一种新的具有脊髓身份的人NSC系（scNSCs）。 3)长期研究将检查scNSCs的成熟，有效性和安全性，我们的领导细胞 脊髓损伤的治疗方法有哪些 4)新的跨突触追踪技术将用于评估两个宿主的突触整合 输入到移植物和移植物输出到宿主运动神经元。